Summary Over 600,000 adults in the US suffer from ESRD. For the appropriate patients, kidney transplantation (KT) reduces mortality, improves quality of life, and saves substantial Medicare dollars. However, selecting patients for KT can be challenging, particularly among certain subgroups such as older adults, and current metrics are of limited utility in informing clinical decision-making. Furthermore, once selected for KT, patients face similar challenges when considering deceased donor offers or deciding if to allow friends or family to put themselves at risk as living donors. Predicting which patients would benefit from KT, and optimally matching them to the right donor, is one of the most critical concerns for patients, transplant physicians, and referring nephrologists. This is a proposal for a K24 Midcareer Investigator Award for Dorry Segev, MD, PhD, an Associate Professor of Surgery and Epidemiology at Johns Hopkins University. Dr. Segev leads three major R01-funded patient- oriented research efforts to address the challenges of ESRD and KT clinical decision-making: (1) A prospective study of frailty and risk prediction among older dialysis patients and kidney transplant recipients; (2) A retrospective study of long-term outcomes and survival benefit from incompatible live donor kidney transplantation; and (3) A multi-center longitudinal study of long-term sequelae of kidney donation. In addition to addressing the aims of the individual grants, these studies provide rich substrate for ancillary studies by mentees, including thousands of patients engaged in several cohorts, as well as many opportunities for advanced methodologic training. Dr. Segev is actively mentoring students, residents, fellows, and junior faculty in an exciting, productive multidisciplinary environment. This K24 will afford future mentees the opportunity to leverage Dr. Segev's rich ongoing research portfolio with the following new aims: (1) To better understand dialysis and KT outcomes important to older adults; (2) To quantify secondary risks of incompatible KT protocols; (3) To elucidate familial, genetic, and non-renal risks after kidney donation; (4) To design models to assist KT candidates with organ offer decisions; and (5) To expand Dr. Segev's capacity to mentor the next generation of clinician-scientists in ESRD and KT by pursuing formal training in mentoring, learning leadership skills from experts at JHU, continuing to foster multidisciplinary collaborations across the institution, connecting with mentors and mentees from across the country, and refining a curriculum for teaching patient-oriented research to surgeons and other clinicians